CA2993451A1 - Methodes permettant de traiter le cancer du pancreas metastatique au moyen de traitements d'association comprenant de l'irinotecan liposomal et de l'oxaliplatine - Google Patents
Methodes permettant de traiter le cancer du pancreas metastatique au moyen de traitements d'association comprenant de l'irinotecan liposomal et de l'oxaliplatine Download PDFInfo
- Publication number
- CA2993451A1 CA2993451A1 CA2993451A CA2993451A CA2993451A1 CA 2993451 A1 CA2993451 A1 CA 2993451A1 CA 2993451 A CA2993451 A CA 2993451A CA 2993451 A CA2993451 A CA 2993451A CA 2993451 A1 CA2993451 A1 CA 2993451A1
- Authority
- CA
- Canada
- Prior art keywords
- oxaliplatin
- irinotecan
- dose
- leucovorin
- nng
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 title claims abstract description 360
- 229960004768 irinotecan Drugs 0.000 title claims abstract description 358
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 title claims abstract description 311
- 229960001756 oxaliplatin Drugs 0.000 title claims abstract description 310
- 206010061289 metastatic neoplasm Diseases 0.000 title claims abstract description 56
- 230000001394 metastastic effect Effects 0.000 title claims abstract description 51
- 206010061902 Pancreatic neoplasm Diseases 0.000 title abstract description 55
- 201000002528 pancreatic cancer Diseases 0.000 title abstract description 55
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 title abstract description 54
- 208000008443 pancreatic carcinoma Diseases 0.000 title abstract description 54
- 238000002648 combination therapy Methods 0.000 title abstract description 14
- 238000000034 method Methods 0.000 title description 39
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 314
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims abstract description 232
- 235000008191 folinic acid Nutrition 0.000 claims abstract description 232
- 239000011672 folinic acid Substances 0.000 claims abstract description 232
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims abstract description 232
- 229960001691 leucovorin Drugs 0.000 claims abstract description 232
- 229960002949 fluorouracil Drugs 0.000 claims abstract description 156
- 238000011282 treatment Methods 0.000 claims abstract description 128
- 210000000496 pancreas Anatomy 0.000 claims abstract description 39
- 208000009956 adenocarcinoma Diseases 0.000 claims abstract description 23
- 238000002560 therapeutic procedure Methods 0.000 claims description 87
- 238000001802 infusion Methods 0.000 claims description 59
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 49
- 238000002512 chemotherapy Methods 0.000 claims description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 3
- 229920002505 N-(Carbonyl-Methoxypolyethylene Glycol 2000)-1,2-Distearoyl-Sn-Glycero-3-Phosphoethanolamine Polymers 0.000 claims description 3
- SRLOHQKOADWDBV-NRONOFSHSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] 2-(2-methoxyethoxycarbonylamino)ethyl phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCCNC(=O)OCCOC)OC(=O)CCCCCCCCCCCCCCCCC SRLOHQKOADWDBV-NRONOFSHSA-M 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims 2
- WEPNHBQBLCNOBB-FZJVNAOYSA-N sucrose octasulfate Chemical compound OS(=O)(=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@H](COS(=O)(=O)O)O[C@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-FZJVNAOYSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 description 72
- 230000001988 toxicity Effects 0.000 description 65
- 231100000419 toxicity Toxicity 0.000 description 65
- 230000002829 reductive effect Effects 0.000 description 49
- 230000009467 reduction Effects 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 36
- 230000004048 modification Effects 0.000 description 35
- 238000012986 modification Methods 0.000 description 35
- 102100029152 UDP-glucuronosyltransferase 1A1 Human genes 0.000 description 33
- 101710205316 UDP-glucuronosyltransferase 1A1 Proteins 0.000 description 33
- 229940079593 drug Drugs 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
- 238000001990 intravenous administration Methods 0.000 description 28
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 25
- 230000004044 response Effects 0.000 description 22
- 229960001592 paclitaxel Drugs 0.000 description 21
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 21
- 108010058566 130-nm albumin-bound paclitaxel Proteins 0.000 description 20
- 206010012735 Diarrhoea Diseases 0.000 description 19
- 208000004235 neutropenia Diseases 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 230000002411 adverse Effects 0.000 description 17
- 150000003839 salts Chemical class 0.000 description 17
- 230000004614 tumor growth Effects 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 16
- 230000004083 survival effect Effects 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 15
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 15
- 231100000226 haematotoxicity Toxicity 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 230000002035 prolonged effect Effects 0.000 description 14
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000011084 recovery Methods 0.000 description 12
- 230000037396 body weight Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 238000011284 combination treatment Methods 0.000 description 10
- KLEAIHJJLUAXIQ-JDRGBKBRSA-N irinotecan hydrochloride hydrate Chemical compound O.O.O.Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 KLEAIHJJLUAXIQ-JDRGBKBRSA-N 0.000 description 10
- 229940048191 onivyde Drugs 0.000 description 10
- 230000003111 delayed effect Effects 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000003442 weekly effect Effects 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 8
- 206010047700 Vomiting Diseases 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- -1 e.g. Chemical compound 0.000 description 8
- 230000002489 hematologic effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000010261 cell growth Effects 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 208000011580 syndromic disease Diseases 0.000 description 7
- 206010061818 Disease progression Diseases 0.000 description 6
- 230000003474 anti-emetic effect Effects 0.000 description 6
- 239000002111 antiemetic agent Substances 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 230000005750 disease progression Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 206010016256 fatigue Diseases 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 5
- 206010048610 Cardiotoxicity Diseases 0.000 description 5
- 208000002633 Febrile Neutropenia Diseases 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 206010037660 Pyrexia Diseases 0.000 description 5
- 229940034982 antineoplastic agent Drugs 0.000 description 5
- 206010003549 asthenia Diseases 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 231100000259 cardiotoxicity Toxicity 0.000 description 5
- 230000007681 cardiovascular toxicity Effects 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 230000007717 exclusion Effects 0.000 description 5
- PJZDLZXMGBOJRF-CXOZILEQSA-L folfirinox Chemical compound [Pt+4].[O-]C(=O)C([O-])=O.[NH-][C@H]1CCCC[C@@H]1[NH-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 PJZDLZXMGBOJRF-CXOZILEQSA-L 0.000 description 5
- 229960005277 gemcitabine Drugs 0.000 description 5
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000002375 Hand-Foot Syndrome Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 206010028813 Nausea Diseases 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000022531 anorexia Diseases 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 206010061428 decreased appetite Diseases 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000008693 nausea Effects 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- 230000002085 persistent effect Effects 0.000 description 4
- 238000009101 premedication Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 229930003347 Atropine Natural products 0.000 description 3
- 208000009079 Bronchial Spasm Diseases 0.000 description 3
- 208000014181 Bronchial disease Diseases 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- 241001643392 Cyclea Species 0.000 description 3
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 3
- 102000003960 Ligases Human genes 0.000 description 3
- 108090000364 Ligases Proteins 0.000 description 3
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- WEPNHBQBLCNOBB-UGDNZRGBSA-N [(2r,3r,4s,5r,6r)-2-[(2s,3s,4r,5r)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate Chemical class OS(=O)(=O)O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](COS(=O)(=O)O)O[C@@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-UGDNZRGBSA-N 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 3
- 229960000396 atropine Drugs 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 229940041216 diphenhydramine hydrochloride 50 mg Drugs 0.000 description 3
- 239000002895 emetic Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- JYEFSHLLTQIXIO-SMNQTINBSA-N folfiri regimen Chemical compound FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 JYEFSHLLTQIXIO-SMNQTINBSA-N 0.000 description 3
- 235000019152 folic acid Nutrition 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000007726 management method Methods 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 3
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- NWVVOUXUHGRCGE-UHFFFAOYSA-N 5-iodo-2,4-dioxo-1h-pyrimidine-6-carboxylic acid Chemical compound OC(=O)C=1NC(=O)NC(=O)C=1I NWVVOUXUHGRCGE-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 238000000959 Cochran–Mantel–Haenszel (CMH) test Methods 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- BCPSLKYBXGKPIW-RTXWKGGWSA-N [(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate [(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.OS(=O)(=O)O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](COS(=O)(=O)O)O[C@@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 BCPSLKYBXGKPIW-RTXWKGGWSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 238000009096 combination chemotherapy Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000005182 global health Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 2
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 230000007056 liver toxicity Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940078646 other antiemetics in atc Drugs 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 238000012447 xenograft mouse model Methods 0.000 description 2
- VVIAGPKUTFNRDU-STQMWFEESA-N (6S)-5-formyltetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1C=O)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-STQMWFEESA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 description 1
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000013392 Carboxylesterase Human genes 0.000 description 1
- 108010051152 Carboxylesterase Proteins 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 208000004766 Cytochrome P-450 CYP2C8 Inducers Diseases 0.000 description 1
- 208000006619 Cytochrome P-450 CYP2C8 Inhibitors Diseases 0.000 description 1
- 208000000130 Cytochrome P-450 CYP3A Inducers Diseases 0.000 description 1
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 1
- 230000000970 DNA cross-linking effect Effects 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 208000008999 Giant Cell Carcinoma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 101100275485 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cox-4 gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007019 Oxalis corniculata Species 0.000 description 1
- 235000016499 Oxalis corniculata Nutrition 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033553 Palmar-plantar erythrodysaesthesia syndrome Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 208000003837 Second Primary Neoplasms Diseases 0.000 description 1
- 208000003252 Signet Ring Cell Carcinoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 229940086245 acetaminophen 650 mg Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 230000003457 anti-vomiting effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- JSRLJPSBLDHEIO-SHYZEUOFSA-N dUMP Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 JSRLJPSBLDHEIO-SHYZEUOFSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000008355 dextrose injection Substances 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 230000023611 glucuronidation Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000009114 investigational therapy Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940008678 levoleucovorin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000000014 lung giant cell carcinoma Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000030314 papillary cystic neoplasm Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000009597 pregnancy test Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 239000012658 prophylactic medication Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000002534 radiation-sensitizing agent Substances 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 201000008123 signet ring cell adenocarcinoma Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 208000019140 solid pseudopapillary neoplasm of the pancreas Diseases 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000013413 tumor xenograft mouse model Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
L'invention concerne des protocoles de traitement d'association comprenant de l'irinotécan liposomal, de l'oxaliplatine et du 5-fluorouracile utilisables dans le traitement du cancer du pancréas, dont le traitement de patients atteints d'un adénocarcinome du pancréas métastatique non traité antérieurement. Le traitement d'association peut comprendre l'administration d'irinotécan liposomal, d'oxaliplatine, de leucovorine et de 5-fluorouracile une fois toutes les deux semaines.
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562208209P | 2015-08-21 | 2015-08-21 | |
| US62/208,209 | 2015-08-21 | ||
| US201562216736P | 2015-09-10 | 2015-09-10 | |
| US62/216,736 | 2015-09-10 | ||
| US201562273244P | 2015-12-30 | 2015-12-30 | |
| US62/273,244 | 2015-12-30 | ||
| US201662281473P | 2016-01-21 | 2016-01-21 | |
| US62/281,473 | 2016-01-21 | ||
| US201662302341P | 2016-03-02 | 2016-03-02 | |
| US62/302,341 | 2016-03-02 | ||
| US201662323245P | 2016-04-15 | 2016-04-15 | |
| US62/323,245 | 2016-04-15 | ||
| US201662343313P | 2016-05-31 | 2016-05-31 | |
| US62/343,313 | 2016-05-31 | ||
| PCT/US2016/047727 WO2017034957A1 (fr) | 2015-08-21 | 2016-08-19 | Méthodes permettant de traiter le cancer du pancréas métastatique au moyen de traitements d'association comprenant de l'irinotécan liposomal et de l'oxaliplatine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2993451A1 true CA2993451A1 (fr) | 2017-03-02 |
Family
ID=58100730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2993451A Pending CA2993451A1 (fr) | 2015-08-21 | 2016-08-19 | Methodes permettant de traiter le cancer du pancreas metastatique au moyen de traitements d'association comprenant de l'irinotecan liposomal et de l'oxaliplatine |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US20170049775A1 (fr) |
| EP (2) | EP3337478B1 (fr) |
| JP (3) | JP2018528185A (fr) |
| KR (1) | KR102714060B1 (fr) |
| CN (1) | CN108495629A (fr) |
| AU (1) | AU2016310476B8 (fr) |
| BR (1) | BR112018002941B1 (fr) |
| CA (1) | CA2993451A1 (fr) |
| ES (1) | ES2826826T3 (fr) |
| HK (1) | HK1257220A1 (fr) |
| IL (1) | IL257149B2 (fr) |
| MX (1) | MX385425B (fr) |
| PT (1) | PT3337478T (fr) |
| RU (1) | RU2747124C2 (fr) |
| SG (1) | SG10201913077QA (fr) |
| SI (1) | SI3337478T1 (fr) |
| TW (5) | TW202400181A (fr) |
| WO (1) | WO2017034957A1 (fr) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
| US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
| JP7113619B2 (ja) * | 2014-12-09 | 2022-08-05 | イプセン バイオファーム リミティド | リポソーマルイリノテカンによる乳がんの治療 |
| US11318131B2 (en) | 2015-05-18 | 2022-05-03 | Ipsen Biopharm Ltd. | Nanoliposomal irinotecan for use in treating small cell lung cancer |
| HK1257216A1 (zh) | 2015-08-20 | 2019-10-18 | 益普生生物制药有限公司 | 使用脂质体伊立替康和parp抑制剂用於癌症治疗的组合疗法 |
| BR112018002941B1 (pt) * | 2015-08-21 | 2023-12-05 | Ipsen Biopharm Ltd | Uso de irinotecano lipossomal, oxaliplatina, leucovorina e 5- fluorouracil no tratamento de primeira linha de adenocarcinoma metastático do pâncreas |
| BR112018006922B1 (pt) | 2015-10-16 | 2023-11-21 | Ipsen Biopharm Ltd | Composições de irinotecano lipossômico estabilizado para armazenamento |
| CN110402163A (zh) | 2016-11-02 | 2019-11-01 | 易普森生物制药有限公司 | 使用包括脂质体伊立替康、奥沙利铂、5-氟尿嘧啶(和甲酰四氢叶酸)的组合疗法治疗胃癌 |
| US12291570B2 (en) * | 2018-10-17 | 2025-05-06 | Biolinerx Ltd. | Treatment of metastatic pancreatic adenocarcinoma |
| WO2020148744A1 (fr) * | 2019-01-17 | 2020-07-23 | Biolinerx Ltd. | Polythérapie pour le traitement du cancer du pancréas |
| US20220072087A1 (en) * | 2019-01-17 | 2022-03-10 | Biolinerx Ltd. | Specific combination therapy for treatment of pancreatic cancer |
| SG11202106435QA (en) * | 2019-02-22 | 2021-07-29 | Novocure Gmbh | Treating gastric cancer using ttfields combined with xelox or folfox |
| CA3157379A1 (fr) * | 2019-10-10 | 2021-04-15 | The University Of North Carolina At Chapel Hill | Complexes de systeme d'administration comprenant un precipite d'un agent actif et procedes d'utilisation |
| EP4355366A4 (fr) * | 2021-06-16 | 2025-05-07 | Fusion Pharmaceuticals Inc. | Combinaison comprenant un composé de liaison au récepteur de la neurotensine et napoli |
| EP4355317A4 (fr) * | 2021-06-16 | 2025-04-30 | Fusion Pharmaceuticals Inc. | Combinaison comprenant un composé de liaison au récepteur de la neurotensine et du napox |
Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| US5077056A (en) | 1984-08-08 | 1991-12-31 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
| JPH0720857B2 (ja) | 1988-08-11 | 1995-03-08 | テルモ株式会社 | リポソームおよびその製法 |
| IL91664A (en) | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5538954A (en) | 1994-06-24 | 1996-07-23 | A/S Dumex (Dumex Ltd.) | Salts of tetracyclines |
| US5783568A (en) | 1994-06-10 | 1998-07-21 | Sugen, Inc. | Methods for treating cancer and other cell proliferative diseases |
| US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
| US5800833A (en) | 1995-02-27 | 1998-09-01 | University Of British Columbia | Method for loading lipid vesicles |
| DE19605024A1 (de) | 1996-01-31 | 1997-08-07 | Schering Ag | Neue selektive Taxane, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung |
| US5997899A (en) | 1996-10-01 | 1999-12-07 | Skyepharma Inc. | Method for producing liposomes with increased percent of compound encapsulated |
| EP0949906A4 (fr) | 1996-10-22 | 2004-11-24 | Hermes Biosciences Inc | Liposomes charges de composes et leurs procedes de preparation |
| US6210707B1 (en) | 1996-11-12 | 2001-04-03 | The Regents Of The University Of California | Methods of forming protein-linked lipidic microparticles, and compositions thereof |
| US6787132B1 (en) | 1997-12-04 | 2004-09-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
| US7244826B1 (en) | 1998-04-24 | 2007-07-17 | The Regents Of The University Of California | Internalizing ERB2 antibodies |
| US6726925B1 (en) | 1998-06-18 | 2004-04-27 | Duke University | Temperature-sensitive liposomal formulation |
| CA2346879A1 (fr) | 1998-09-16 | 2000-04-27 | Alza Corporation | Inhibiteurs de topoisomerase pieges dans des liposomes |
| US7311924B2 (en) | 1999-04-01 | 2007-12-25 | Hana Biosciences, Inc. | Compositions and methods for treating cancer |
| WO2000066125A1 (fr) | 1999-04-29 | 2000-11-09 | Aventis Pharma S.A. | Procede de traitement du cancer a l'aide de derives de la camptothecine et de 5-fluorouracil |
| US6720001B2 (en) | 1999-10-18 | 2004-04-13 | Lipocine, Inc. | Emulsion compositions for polyfunctional active ingredients |
| US6511676B1 (en) | 1999-11-05 | 2003-01-28 | Teni Boulikas | Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes |
| ATE341310T1 (de) | 2000-02-04 | 2006-10-15 | Lipoxen Technologies Ltd | Dehydratisierungs-/rehydratisierungsverfahren zur herstellung von liposome |
| US6545010B2 (en) | 2000-03-17 | 2003-04-08 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer |
| JP4679028B2 (ja) | 2000-05-15 | 2011-04-27 | セルジーン コーポレイション | 結腸直腸癌を治療するための組成物および方法 |
| AU7038501A (en) | 2000-06-30 | 2002-01-14 | Inex Pharmaceuticals Corp | Liposomal antineoplastic drugs and uses thereof |
| TWI283575B (en) | 2000-10-31 | 2007-07-11 | Eisai Co Ltd | Medicinal compositions for concomitant use as anticancer agent |
| JP2004525138A (ja) | 2001-03-26 | 2004-08-19 | アルザ・コーポレーシヨン | 治療剤の改良された細胞内送達のためのリポソーム組成物 |
| US7219016B2 (en) | 2001-04-20 | 2007-05-15 | Yale University | Systems and methods for automated analysis of cells and tissues |
| WO2003030864A1 (fr) | 2001-05-29 | 2003-04-17 | Neopharm, Inc. | Formulation liposomale d'irinotecan |
| JP2005504759A (ja) | 2001-07-23 | 2005-02-17 | エピダウロス・バイオテクノロジー・アクチェンゲゼルシャフト | Ｃｙｐ３ａ５に基づいたがんの改善治療の手段及び方法 |
| US7850990B2 (en) | 2001-10-03 | 2010-12-14 | Celator Pharmaceuticals, Inc. | Compositions for delivery of drug combinations |
| AU2003237864B2 (en) | 2002-05-15 | 2008-12-18 | California Pacific Medical Center | Delivery of nucleic acid-like compounds |
| WO2003101475A1 (fr) | 2002-05-31 | 2003-12-11 | Transmolecular Inc. | Traitement de troubles de proliferation cellulaire au moyen de la chlorotoxine |
| WO2004035032A2 (fr) | 2002-08-20 | 2004-04-29 | Neopharm, Inc. | Formulation de sn-38 a base de lipides pharmaceutiquement actifs |
| RS20150135A1 (sr) | 2003-05-30 | 2015-08-31 | Genentech Inc. | Tretman sa anti-vegf antitelima |
| RU2424792C2 (ru) | 2004-05-03 | 2011-07-27 | Хермес Байесайенсиз, Инк. | Липосомы, используемые для доставки лекарственных средств |
| US8658203B2 (en) | 2004-05-03 | 2014-02-25 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for drug delivery to the brain |
| AP2255A (en) | 2004-06-01 | 2011-07-21 | Yakult Honsha Kk | Irinotecan preparation. |
| JP2006248978A (ja) | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
| TWI375673B (en) | 2005-04-11 | 2012-11-01 | Abbott Lab | 1h-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent parp inhibitors |
| EP1951239A2 (fr) | 2005-10-25 | 2008-08-06 | Celator Pharmaceuticals, Inc. | Traitement a base de combinaisons de medicaments a rapport fixe pour le traitement de tumeurs solides |
| WO2007076117A2 (fr) | 2005-12-22 | 2007-07-05 | Celator Pharmaceuticals, Inc. | Formulations liposomales composées d'amines secondaires et tertiaires et procédés de préparation desdites formulations |
| PL2338487T3 (pl) | 2006-01-17 | 2014-03-31 | Abbvie Bahamas Ltd | Terapia skojarzona z inhibitorami PARP |
| WO2007109184A2 (fr) | 2006-03-16 | 2007-09-27 | Bionumerik Pharmaceuticals, Inc. | Composés augmentant l'activité anticancéreuse, formulations les contenant et leurs méthodes d'utilisation |
| HRP20131113T1 (hr) | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| US20120003160A1 (en) | 2007-06-29 | 2012-01-05 | Amag Pharmaceuticals, Inc. | Macrophage-Enhanced MRI (MEMRI) in a Single Imaging Session |
| ES2550759T3 (es) | 2007-08-17 | 2015-11-12 | Celator Pharmaceuticals, Inc. | Formulaciones farmacológicas de platino mejoradas |
| EP2197917A1 (fr) | 2007-09-28 | 2010-06-23 | Universitätsspital Basel | Immunoliposomes utilisés pour le traitement du cancer |
| NZ586123A (en) | 2007-11-12 | 2012-12-21 | Bipar Sciences Inc | Treatment of ovarian cancer with 4-iodo-3-nitrobenzamide in combination with topoisomerase inhibitors |
| CA2708157A1 (fr) | 2007-12-07 | 2009-06-11 | Bipar Sciences, Inc. | Traitement du cancer avec des combinaisons d'inhibiteurs de topoisomerase et d'inhibiteurs de parp |
| US20110104256A1 (en) | 2008-03-25 | 2011-05-05 | Yaolin Wang | Methods for treating or preventing colorectal cancer |
| US8067432B2 (en) | 2008-03-31 | 2011-11-29 | University Of Kentucky Research Foundation | Liposomal, ring-opened camptothecins with prolonged, site-specific delivery of active drug to solid tumors |
| MX2010011145A (es) | 2008-04-11 | 2011-04-11 | Merrimack Pharmaceuticals Inc | Enlazadores de la albumina de suero humana y conjugados de la misma. |
| US8852630B2 (en) | 2008-05-13 | 2014-10-07 | Yale University | Chimeric small molecules for the recruitment of antibodies to cancer cells |
| US20100022444A1 (en) * | 2008-07-24 | 2010-01-28 | Bodybio, Inc. | Combination therapy for modulation of activity and development of cells and tissues |
| CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| JP2012525371A (ja) * | 2009-05-01 | 2012-10-22 | オンコザイム・ファーマ・インコーポレイテッド | 癌を治療するためのペンタミジンの組み合わせ |
| ES2547698T3 (es) | 2009-12-03 | 2015-10-08 | Jiangsu Hengrui Medicine Co., Ltd. | Liposoma de irinotecán o su clorhidrato y método de preparación del mismo |
| EP2575804A4 (fr) | 2010-06-04 | 2013-10-23 | Abraxis Bioscience Llc | Procédés de traitement du cancer du pancréas |
| EP2595618A1 (fr) | 2010-07-19 | 2013-05-29 | BiPar Sciences, Inc. | Méthodes de traitement du cancer du sein utilisant le 4-iodo-3-nitrobenzamide en association avec des agents anticancéreux |
| CA2806076A1 (fr) | 2010-07-22 | 2012-01-26 | The Regents Of The University Of California | Anticorps-antigenes antitumoraux et methodes d'utilisation correspondantes |
| RU2541100C2 (ru) * | 2010-09-03 | 2015-02-10 | Боард Оф Регентс Оф Зе Юниверсити Оф Небраска | Способ и композиция для лечения рака |
| JP6208582B2 (ja) | 2010-12-06 | 2017-10-04 | メリマック ファーマシューティカルズ インコーポレーティッド | アントラサイクリン系化学療法剤を含有しているｅｒｂｂ２標的免疫リポソームによる治療における心臓毒性を抑制するための用量及び投与 |
| US9226984B2 (en) | 2010-12-14 | 2016-01-05 | Technical University of Denmark and Rigshospitalet | Entrapment of radionuclides in nanoparticle compositions |
| WO2012112730A2 (fr) | 2011-02-15 | 2012-08-23 | Merrimack Pharmaceuticals, Inc. | Compositions et procédés pour délivrer un acide nucléique à une cellule |
| HRP20170713T1 (hr) | 2011-04-19 | 2017-07-14 | Merrimack Pharmaceuticals, Inc. | Bispecifično anti-igf-1r i anti-erbb3 antitijelo |
| JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
| US8691231B2 (en) | 2011-06-03 | 2014-04-08 | Merrimack Pharmaceuticals, Inc. | Methods of treatment of tumors expressing predominantly high affinity EGFR ligands or tumors expressing predominantly low affinity EGFR ligands with monoclonal and oligoclonal anti-EGFR antibodies |
| AU2013201584A1 (en) | 2012-03-12 | 2013-09-26 | Merrimack Pharmaceuticals, Inc. | Methods for treating pancreatic cancer using combination therapies comprising an anti-ErbB3 antibody |
| WO2013158803A1 (fr) | 2012-04-17 | 2013-10-24 | Merrimack Pharmaceuticals, Inc. | Compositions et procédés pour une imagerie non invasive |
| US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
| AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
| WO2014113167A1 (fr) | 2012-12-14 | 2014-07-24 | Merrimack Pharmaceuticals, Inc. | Procédés d'imagerie non-invasive destinés à la sélection de patients pour un traitement au moyen d'agents thérapeutiques nanoparticulaires |
| UA117581C2 (uk) | 2013-03-27 | 2018-08-27 | Тайхо Фармасьютікал Ко., Лтд. | Протипухлинний лікарський засіб, який включає низькодозований гідрохлориду іринотекану гідрат |
| WO2015031536A1 (fr) | 2013-08-27 | 2015-03-05 | Northeastern University | Système de délivrance de médicament nanoparticulaire et procédé de traitement du cancer et d'un traumatisme neurologique |
| US20160303264A1 (en) | 2013-10-23 | 2016-10-20 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for non-invasive imaging and drug delivery |
| JP7113619B2 (ja) | 2014-12-09 | 2022-08-05 | イプセン バイオファーム リミティド | リポソーマルイリノテカンによる乳がんの治療 |
| WO2016168451A1 (fr) | 2015-04-14 | 2016-10-20 | Merrimack Pharmaceuticals, Inc. | Compositions pour l'amélioration de la pharmacocinétique et de l'indice thérapeutique d'un traitement du cancer |
| HK1257216A1 (zh) | 2015-08-20 | 2019-10-18 | 益普生生物制药有限公司 | 使用脂质体伊立替康和parp抑制剂用於癌症治疗的组合疗法 |
| BR112018002941B1 (pt) * | 2015-08-21 | 2023-12-05 | Ipsen Biopharm Ltd | Uso de irinotecano lipossomal, oxaliplatina, leucovorina e 5- fluorouracil no tratamento de primeira linha de adenocarcinoma metastático do pâncreas |
| BR112018006922B1 (pt) | 2015-10-16 | 2023-11-21 | Ipsen Biopharm Ltd | Composições de irinotecano lipossômico estabilizado para armazenamento |
| US20170202840A1 (en) | 2016-01-14 | 2017-07-20 | Merrimack Pharmaceuticals, Inc. | Treatment of pancreatic cancer with liposomal irinotecan |
| WO2017172678A1 (fr) | 2016-03-30 | 2017-10-05 | Merrimack Pharmaceuticals, Inc. | Méthodes de traitement du cancer à l'aide de polythérapies comprenant une préparation d'anticorps anti-egfr oligoclonal et de l'irinotécan lipsomal |
| US20170333421A1 (en) | 2016-05-18 | 2017-11-23 | Ipsen Biopharm Ltd. | Population Pharmacokinetics of Liposomal Irinotecan |
| MA45046A (fr) | 2016-05-18 | 2019-03-27 | Ipsen Biopharm Ltd | Irinotécan nanoliposomal utilisé dans le traitement du cancer bronchique à petites cellules |
| CN106420789A (zh) * | 2016-10-08 | 2017-02-22 | 中国人民解放军总医院 | 复发耐药消化道肿瘤地西他滨综合治疗方案 |
| CN110402163A (zh) | 2016-11-02 | 2019-11-01 | 易普森生物制药有限公司 | 使用包括脂质体伊立替康、奥沙利铂、5-氟尿嘧啶(和甲酰四氢叶酸)的组合疗法治疗胃癌 |
-
2016
- 2016-08-19 BR BR112018002941-6A patent/BR112018002941B1/pt active IP Right Grant
- 2016-08-19 PT PT167583376T patent/PT3337478T/pt unknown
- 2016-08-19 EP EP16758337.6A patent/EP3337478B1/fr active Active
- 2016-08-19 CN CN201680046873.3A patent/CN108495629A/zh active Pending
- 2016-08-19 JP JP2018506600A patent/JP2018528185A/ja not_active Withdrawn
- 2016-08-19 KR KR1020187005220A patent/KR102714060B1/ko active Active
- 2016-08-19 TW TW112110238A patent/TW202400181A/zh unknown
- 2016-08-19 MX MX2018001802A patent/MX385425B/es unknown
- 2016-08-19 TW TW111103869A patent/TW202243677A/zh unknown
- 2016-08-19 RU RU2018105666A patent/RU2747124C2/ru active
- 2016-08-19 TW TW105126833A patent/TWI778942B/zh active
- 2016-08-19 WO PCT/US2016/047727 patent/WO2017034957A1/fr not_active Ceased
- 2016-08-19 SI SI201630927T patent/SI3337478T1/sl unknown
- 2016-08-19 US US15/241,106 patent/US20170049775A1/en not_active Abandoned
- 2016-08-19 CA CA2993451A patent/CA2993451A1/fr active Pending
- 2016-08-19 ES ES16758337T patent/ES2826826T3/es active Active
- 2016-08-19 SG SG10201913077QA patent/SG10201913077QA/en unknown
- 2016-08-19 EP EP20190127.9A patent/EP3791876A1/fr active Pending
- 2016-08-19 TW TW113117993A patent/TW202508602A/zh unknown
- 2016-08-19 TW TW109134982A patent/TW202126293A/zh unknown
- 2016-08-19 IL IL257149A patent/IL257149B2/en unknown
- 2016-08-19 HK HK18116225.3A patent/HK1257220A1/zh unknown
- 2016-08-19 AU AU2016310476A patent/AU2016310476B8/en active Active
-
2017
- 2017-11-10 US US15/809,815 patent/US11344552B2/en active Active
-
2021
- 2021-10-28 JP JP2021176412A patent/JP7463329B2/ja active Active
-
2022
- 2022-04-01 US US17/711,500 patent/US20230062425A1/en not_active Abandoned
-
2024
- 2024-02-16 JP JP2024022222A patent/JP2024045587A/ja active Pending
- 2024-05-29 US US18/676,591 patent/US20240358706A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240358706A1 (en) | Methods for Treating Metastatic Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan and Oxaliplatin | |
| AU2017354903B2 (en) | Treating gastric cancer using combination therapies comprising liposomal irinotecan, oxaliplatin, 5-fluoruracil (and leucovorin) | |
| US20250381191A1 (en) | Methods for Treating Metastatic Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan and Oxaliplatin | |
| HK40045473A (en) | Methods for treating metastatic pancreatic cancer using combination therapies comprising liposomal irinotecan and oxaliplatin | |
| HK1257250B (en) | Drug combination comprising liposomal irinotecan, oxaliplatin, 5-fluorouracil and leucovorin for treating metastatic pancreatic cancer | |
| HK40009222A (en) | Treating gastric cancer using combination therapies comprising liposomal irinotecan, oxaliplatin, 5-fluoruracil (and leucovorin) | |
| Huang et al. | Decreasing dosage of irinotecan, 5-flurouracil (5-FU) and leucovorin (LV) in the treatment of advanced and/or metastatic colorectal cancer: a phase II study |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |